Multifunctional nanoparticles as a tissue adhesive and an injectable marker for image-guided procedures

Tissue adhesives have emerged as an alternative to sutures and staples for wound closure and reconnection of injured tissues after surgery or trauma. Owing to their convenience and effectiveness, these adhesives have received growing attention particularly in minimally invasive procedures. For safe and accurate applications, tissue adhesives should be detectable via clinical imaging modalities and be highly biocompatible for intracorporeal procedures. However, few adhesives meet all these requirements. Herein, we show that biocompatible tantalum oxide/silica core/shell nanoparticles (TSNs) exhibit not only high contrast effects for real-time imaging but also strong adhesive properties. Furthermore, the biocompatible TSNs cause much less cellular toxicity and less inflammation than a clinically used, imageable tissue adhesive (that is, a mixture of cyanoacrylate and Lipiodol). Because of their multifunctional imaging and adhesive property, the TSNs are successfully applied as a hemostatic adhesive for minimally invasive procedures and as an immobilized marker for image-guided procedures.

Tumoral LINE-1 hypomethylation is associated with poor survival of patients with intrahepatic cholangiocarcinoma

ECC: Extrahepatic cholangiocarcinoma; ICC: Intrahepatic cholangiocarcinoma; IG: Intraductal growth; LINE-1: Long interspersed element-1; MF: Mass-forming; PI: Periductal infiltrative; TNM: Tumor, node, and metastasisAbstract Background DNA methylation changes occurring in cancer cells are featured with both promoter CpG island hypermethylation and diffuse genomic hypomethylation. Long interspersed element-1 (LINE-1) is repeated in an interspersed manner with an estimated 500,000 copies per genome. LINE-1 has its CpG sites of the 5′ untranslated region methylated heavily in normal cells and undergoes demethylation in association with cancerization. However, little information is available regarding LINE-1 hypomethylation and its prognostic implication in intrahepatic cholangiocarcinomas. Methods A total of 172 cases of intrahepatic cholangiocarcinomas were analyzed for their methylation levels at four CpG sites of LINE-1 using bisulfite pyrosequencing. We examined the relation between tumoral LINE-1 methylation level and clinicopathological features, including survival. Results Tumor differentiation, lymphatic invasion, and T stage were associated with a low average methylation level of LINE-1 at the four CpG sites; LINE-1 methylation level tended to be lower in high-grade differentiation, lymphatic emboli, and higher T stage. LINE-1 hypomethylation was significantly linked with lower cancer-specific survival in patients with intrahepatic cholangiocarcinoma and was found to be an independent prognostic parameter. Conclusions Our findings suggest that tumoral LINE-1 hypomethylation could be a molecular biomarker heralding poor prognosis of patients with intrahepatic cholangiocarcinoma. Our findings need to be validated in further study.This work was supported by a grant from the National Research Foundation (NRF) grants funded by the Korean Ministry of Science, ICT and Future Planning (2011–0030049 and 2016M3A9B6026921), a grant from the Priority Research Centers Program through the NRF (2009–0093820), and a grant from the Korea Health Technology R & D Project through the Korea Health Industry Development Institute funded by the Korean Ministry of Health and Welfare (HI14C1277). The funding bodies had no role in the design of the study, the collection, analysis, and interpretation of the data, or in the writing of the manuscript

Tenofovir-associated nephrotoxicity in patients with chronic hepatitis B: two cases

Tenofovir disoproxil fumarate (TDF) is effective against chronic hepatitis B (CHB) infection and its use is increasing rapidly worldwide. However, it has been established that TDF is associated with renal toxicity in human immunodeficiency virus-infected patients, while severe or symptomatic TDF-associated nephrotoxicity has rarely been reported in patients with CHB. Here we present two patients with TDF-associated nephrotoxicity who were being treated for CHB infection. The first patient was found to have clinical manifestations of proximal renal tubular dysfunction and histopathologic evidence of acute tubular necrosis at 5 months after starting TDF treatment. The second patient developed acute kidney injury at 17 days after commencing TDF, and he was found to have membranoproliferative glomerulonephritis with acute tubular injury. The renal function improved in both patients after discontinuing TDF. We discuss the risk factors for TDF-associated renal toxicity and present recommendations for monitoring renal function during TDF therapy

MEST-C pathological score and long-term outcomes of child and adult patients with Henoch-Schönlein purpura nephritis

Henoch-Schönlein purpura nephritis (HSPN), a small-vessel vasculitis, shares renal pathological features with immunoglobulin A nephropathy. Oxford classification of immunoglobulin A nephropathy pathology has been updated to the MEST-C score, but its application in HSPN remains unresolved. Two hundred and thirteen patients with biopsy-proven HSPN were retrieved from the Seoul National University Hospital between 2000 and 2017. Renal outcome risks (i.e., end-stage renal disease or doubling of serum creatinine) were evaluated according to MEST-C scores after stratification by age: 113 children aged < 18 years (9.2 ± 3.6 years) and 100 adults aged ≥18 years (38.6 ± 18.3 years). We pooled our data with four previous cohort studies in which MEST or MEST-C scores were described in detail. Twenty-one child (19%) and 16 adult (16%) patients reached the renal outcome during the median follow-up periods of 12 years and 13 years, respectively (maximum 19 years). In children, M1 and T1/T2 scores revealed worse renal outcomes than did M0 and T0 scores, respectively, whereas the T score was the only factor related to worse outcomes in adult patients after adjusting for multiple clinical and laboratory variables. The pooled data showed that M1, S1, and T1/T2 in children and E1 and T1/T2 in adults were correlated with poorer renal outcomes than those of their counterpart scores. The Oxford classification MEST-C scores can predict long-term renal outcomes in patients with HSPN.This work was supported by a grant from the Basic Science Research Program through the National Research Foundation of Korea (NRF) funded by the Ministry of Education (NRF-2017R1D1A1B03031642), which had no role in the study design, data collection, analysis, interpretation, or manuscript writing

PAIP 2019: Liver cancer segmentation challenge

Pathology Artificial Intelligence Platform (PAIP) is a free research platform in support of pathological artificial intelligence (AI). The main goal of the platform is to construct a high-quality pathology learning data set that will allow greater accessibility. The PAIP Liver Cancer Segmentation Challenge, organized in conjunction with the Medical Image Computing and Computer Assisted Intervention Society (MICCAI 2019), is the first image analysis challenge to apply PAIP datasets. The goal of the challenge was to evaluate new and existing algorithms for automated detection of liver cancer in whole-slide images (WSIs). Additionally, the PAIP of this year attempted to address potential future problems of AI applicability in clinical settings. In the challenge, participants were asked to use analytical data and statistical metrics to evaluate the performance of automated algorithms in two different tasks. The participants were given the two different tasks: Task 1 involved investigating Liver Cancer Segmentation and Task 2 involved investigating Viable Tumor Burden Estimation. There was a strong correlation between high performance of teams on both tasks, in which teams that performed well on Task 1 also performed well on Task 2. After evaluation, we summarized the top 11 team&apos;s algorithms. We then gave pathological implications on the easily predicted images for cancer segmentation and the challenging images for viable tumor burden estimation. Out of the 231 participants of the PAIP challenge datasets, a total of 64 were submitted from 28 team participants. The submitted algorithms predicted the automatic segmentation on the liver cancer with WSIs to an accuracy of a score estimation of 0.78. The PAIP challenge was created in an effort to combat the lack of research that has been done to address Liver cancer using digital pathology. It remains unclear of how the applicability of AI algorithms created during the challenge can affect clinical diagnoses. However, the results of this dataset and evaluation metric provided has the potential to aid the development and benchmarking of cancer diagnosis and segmentation. (C) 2020 The Authors. Published by Elsevier B.V

Improving the Accuracy of Intrahepatic Cholangiocarcinoma Subtype Classification by Hidden Class Detection via Label Smoothing

Obtaining ground-truth labels for supervised training is a labor-intensive and time-consuming task. Owning to their large size, only slide-level labels or a handful of coarse annotations are usually provided for pathology images, which makes the training of the classifier challenging. In this study, we propose a conceptually simple, two-stage approach to classify small and large duct types in intrahepatic chalongiocarcinoma using only slide-level labels. Unlike conventional pathology image analysis methods employ multiple instance learning (MTh) applied to overcome the problem of the slide-level label, we introduce a novel label smoothing method to progressively refine the training labels to improve the classification accuracy. The main idea is that we introduce the hidden class, which is assumed to be mutually inclusive of all ground-truth classes and less confident for classification. By iteratively refining (i.e., smoothing) per-patch labels, we can extract and discard the hidden class from the training data. We demonstrate that the proposed label filtering scheme improves the classification accuracy by up to 30% compared to the baseline MTh method and 10% compared to the state-of-the-art noisy label cleaning method. In addition, we demonstrate the effectiveness of gene mutation prior information in the classification of two different duct types. The experimental results suggest that the proposed method may provide pathologists insight into the study of correlations between genetic and histologic subtypes.N

Quantitative analysis of tendon histopathology using digital pathology in rat models with Achilles tendon injury

© 2022 Informa UK Limited, trading as Taylor &amp; Francis Group.Although digital image analysis methods that quantify histopathologic features have emerged, no validated quantitative methods are available to evaluate tendon injury. This study aimed to propose and validate a quantitative analysis method to identify the histopathologic features of tendon injuries. The histopathologic features of two Achilles tendon injury models (a partial full-thickness defect model and a collagenase injection model) using Sprague-Dawley rats were evaluated by semiquantitative grading and a quantitative analysis method using a digital pathology software at weeks 1 and 4 after tendon injury (six tendons per group at each time point). The outcome variables between tendon injury models and between time points were compared, and the correlation between semiquantitative scores and the results of the quantitative analysis was investigated. The proposed analysis method quantified the severity of the histopathological features after tendon injury. Quantitative analysis differentiated the cell morphology between tendon injury models and time points better than semiquantitative scoring. The results from quantitative measurements correlated significantly with the semiquantitative scores. The proposed quantitative method can be effective in evaluating the histopathology of tendon injuries.N

Duodenal Adenocarcinoma of Brunner Gland Origin: A Case Report

We report a case of adenocarcinoma originating from the duodenal Brunner glands in a 47-year-old female patient. The lesion was 0.8 cm in extent and located at the posterior wall of the first part of the duodenum. Histologically, the tumor showed transition from non-neoplastic Brunner glands through dysplastic epithelium into adenocarcinoma. The carcinoma cells were strongly positive for MUC6 protein, which is an epithelial marker for the Brunner glands. Tumor protein p53 was overexpressed in the carcinoma cells, but not in the non-neoplastic or dysplastic epithelium. Dystrophic calcification was predominant. This is the first case report of duodenal adenocarcinoma of Brunner gland origin in Korea

Increased Intratumoral Lymphatic Vessel Density Correlates with Lymph Node Metastasis in Early Gastric Carcinoma

Prediction of lymph node metastasis in early gastric carcinoma (EGC) is important for management and follow-up of EGC patients. Increased lymphangiogenesis has been suggested to correlate with lymphatic invasion and lymph node metastasis in various tumors. Lymphatic vessel density (LVD) and microvessel density (MVD) of 141 EGCs were determined by double immunohistochemical staining for D2-40 and CD31. The mean values of three to five hotspots were calculated in intratumoral and peritumoral areas in digital images. The mean value of intratumoral LVD in a lymph-node-positive EGC group was 28.24/field, which was significantly higher than in a lymph-node-negative EGC group (19.43/field, P = 0.005). Peritumoral LVD, intratumoral MVD, and peritumoral MVD did not correlate with lymph node metastasis in EGCs (P > 0.05). Intratumoral LVD did not show significant differences according to lymphatic invasion and differentiation, which were positive predictors for lymph node metastasis in EGC. Using multivariate logistic regression, intratumoral LVD was an independent factor, with the above two factors and depth of invasion, for the prediction of lymph node metastasis in EGC with a relative risk of 3.570 in high-intratumoral-LVD group compared with low-intratumoral-LVD group (P = 0.022). Intratumoral LVD may be a useful, independent predictor for lymph node metastasis, especially in combination with previously established predictors in EGC.Zhao D, 2008, J ORAL PATHOL MED, V37, P616, DOI 10.1111/j.1600-0714.2008.00707.xInoue A, 2008, PATHOL INT, V58, P611, DOI 10.1111/j.1440-1827.2008.02279.xGao P, 2008, CANCER LETT, V263, P223, DOI 10.1016/j.canlet.2008.01.017El-Gohary YM, 2008, AM J CLIN PATHOL, V129, P578, DOI 10.1309/2HGNJ1GU57JMBJAQAn JY, 2007, ANN SURG, V246, P749, DOI 10.1097/SLA.0b013e31811f3fb7Longatto A, 2007, GYNECOL ONCOL, V107, P45, DOI 10.1016/j.ygyno.2007.05.029Ishikawa S, 2007, GASTRIC CANCER, V10, P35, DOI 10.1007/s10120-006-0407-2Kaneko I, 2007, DIS COLON RECTUM, V50, P13, DOI 10.1007/s10350-006-0745-5YUANMING L, 2007, ARCH MED RES, V38, P106Ding SG, 2006, HUM PATHOL, V37, P861, DOI 10.1016/j.humpath.2006.02.006Liang P, 2006, VIRCHOWS ARCH, V448, P570, DOI 10.1007/s00428-006-0166-9Roma AA, 2006, MODERN PATHOL, V19, P392, DOI 10.1038/modpathol.3800546Nakamura Y, 2006, J CLIN PATHOL, V59, P77, DOI 10.1136/jcp.2005.028779SAKO A, 2006, GASTRIC CANCER, V9, P295Gombos Z, 2005, CLIN CANCER RES, V11, P8364, DOI 10.1158/1078-0432.CCR-05-1238Evangelou E, 2005, MODERN PATHOL, V18, P1490, DOI 10.1038/modpathol.3800457Van der Auwera I, 2005, CLIN CANCER RES, V11, P7637, DOI 10.1158/1078-0432.CCR-05-1142Cao YH, 2005, NAT REV CANCER, V5, P735, DOI 10.1038/nrc1693Kitadai Y, 2005, INT J CANCER, V115, P388, DOI 10.1002/ijc.20859LIU HD, 2005, AI ZHENG, V24, P699Yokota T, 2004, SCAND J GASTROENTERO, V39, P380, DOI 10.1080/00365520310008629*JAP GASTR CANC AS, 2004, TREAT GUID GASTR CARHall FT, 2003, ARCH OTOLARYNGOL, V129, P716Williams CSM, 2003, J PATHOL, V200, P195, DOI 10.1002/path.1343Maula SM, 2003, CANCER RES, V63, P1920Mazumdar M, 2003, STAT MED, V22, P559, DOI 10.1002/sim.1333Straume O, 2003, CLIN CANCER RES, V9, P250Folli S, 2001, JPN J CLIN ONCOL, V31, P495Yokota T, 2001, INT SURG, V86, P206Maehara Y, 2000, SURGERY, V128, P408, DOI 10.1067/msy.2000.107265Che XM, 1998, CHINESE MED J-PEKING, V111, P1090ALTMAN DG, 1994, J NATL CANCER I, V86, P829MIETTINEN M, 1994, MODERN PATHOL, V7, P82WEIDNER N, 1991, NEW ENGL J MED, V324, P1LISTROM MB, 1987, GASTROENTEROLOGY, V93, P506

A case of gemcitabine-induced thrombotic microangiopathy in a urothelial tumor patient with a single kidney

Thrombotic microangiopathy (TMA) is a rare complication of gemcitabine treatment. A 55-year-old man with a history of urothelial cancer underwent right ureteronephrectomy and palliative chemotherapy. The patient presented with dyspnea, generalized edema with foamy urine, and new-onset hypertension with acute kidney injury (AKI). Although AKI with oliguria was evident, thrombocytopenia and hemolytic anemia were not overt. To determine the cause of rapidly progressive azotemia, kidney biopsy was performed despite a single kidney and revealed chronic TMA. Microangiopathic hemolytic anemia and thrombocytopenia developed after renal biopsy. Diagnosed as gemcitabine-induced TMA, gemcitabine cessation and active treatment including steroids, plasmapheresis, and rituximab were carried out, but the patient׳s condition progressed to a dialysis-dependent state. Gemcitabine-induced TMA is often difficult to diagnose because of its variable clinical course. Therefore, heightened awareness of this potentially lethal complication of gemcitabine is essential; renal biopsy may be helpful